{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T11:20:42Z","timestamp":1718882442638},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2009,10,28]],"date-time":"2009-10-28T00:00:00Z","timestamp":1256688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2010,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pheochromocytomas are neoplasias of neural crest origin that arise from the chromaffin cells of the adrenal medulla. Pheochromocytomas arise with complete penetrance in rats homozygous for a germ\u2010line frameshift mutation of <jats:italic>Cdkn1b<\/jats:italic>, encoding the cell cycle inhibitor p27KIP1 (MENX syndrome). We performed a genome\u2010wide scan for allelic imbalance comparing 20 rat pheochromocytoma DNAs with normal rat DNA to better understand the pathobiology of the tumors and to correlate the findings with human pheochromocytoma. We identified allelic imbalance (AI) at candidate regions on rat chromosomes 8 and 19. Interestingly, the regions often lost in rat tumors are syntenic to regions involved in human pheochromocytomas. Fluorescence <jats:italic>in situ<\/jats:italic> hybridization analysis further validated the AI data. <jats:italic>Sdhd<\/jats:italic> and <jats:italic>Rassf1a<\/jats:italic> were analyzed in detail as they map to regions of AI on chromosome 8 and their homologues are implicated in human pheochromocytoma: we found no genetic mutations nor decreased expression. We also analyzed additional candidate genes, that is, rat homologues of genes predisposing to human pheochromocytoma and known tumor\u2010suppressor genes, but we found no AI. In contrast, we observed frequent overexpression of <jats:italic>Cdkn2a<\/jats:italic> and <jats:italic>Cdkn2c<\/jats:italic>, encoding the cell cycle inhibitors p16INK4a and p18INK4c, respectively. The relative small number of allelic changes we found in rat pheochromocytoma might be related to their nonmalignant status and losses at chromosomes 8 and 19 are events that precede malignancy. Because of the high concordance of affected loci between rat and human tumors, studies of the MENX\u2010associated pheochromocytomas should facilitate the identification of novel candidate genes implicated in their human counterpart.<\/jats:p>","DOI":"10.1002\/ijc.24925","type":"journal-article","created":{"date-parts":[[2009,10,29]],"date-time":"2009-10-29T20:38:22Z","timestamp":1256848702000},"page":"2362-2372","source":"Crossref","is-referenced-by-count":7,"title":["Allelic loss of chromosomes 8 and 19 in MENX\u2010associated rat 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